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Hsa_circ_0008945 promoted breast cancer progression by targeting miR-338-3p

Authors Zhang L, Ding F

Received 30 April 2019

Accepted for publication 22 July 2019

Published 16 August 2019 Volume 2019:12 Pages 6577—6589

DOI https://doi.org/10.2147/OTT.S213994

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Li Zhang, Fengping Ding

Department of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, Xinchang, Zhejiang, People’s Republic of China

Correspondence: Li Zhang
Department of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, 117 Gushan Middle Road, Nanming Street, Xinchang 312500, People’s Republic of China
Tel +86 1 895 756 8155
Email lizhang78@126.com

Purpose: To detect the expression and function of circ_0008945 in breast cancer (BC) and to explore its potential molecular mechanisms in BC tumorigenesis.
Materials and methods: We measured expression levels of circ_0008945, miR-338-3p and homeobox A3 (HOXA3) in BC tissue specimens and cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). We examined the effects of all three genes on BC cell proliferation using Cell Counting Kit-8 (CCK-8) and colony formation assays. We also performed a Transwell assay to assess the migratory and invasive ability of treated BC cells. BC cell apoptosis was assessed using flow cytometric (FCM) analysis; interaction between miR-338-3p and circ_0008945 or HOXA3 was verified by dual-luciferase reporter assay as well as by ribonucleic-acid (RNA) pulldown. Finally, we used an in vivo tumor growth assay to assess the role of circ_0008945 overexpression in BC tumor growth.
Results: We found that circ_0008945 expression was significantly increased in both BC tissue specimens and cells. This increase was correlated with poor prognosis in BC patients. Knockdown of circ_0008945 inhibited BC cell proliferation, migration and invasion while promoting BC cell apoptosis in vitro. Overexpression of circ_0008945 remarkably promoted BC tumor growth in vivo. Mechanistically, circ_0008945 acted as a miRNA sponge for miR-338-3p and inhibited its expression in BC cells. Moreover, miR-338-3p targeted and inhibited HOXA3.
Conclusion: We found that circ_0008945 acted as a BC oncogene by physically binding miR-338-3p, which further targeted and regulated HOXA3.

Keywords: apoptosis, breast cancer, circ_0008945, miR-338-3p, proliferation

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